Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of (1-desamino-8-D-arginine) vasopressin (dDAVP) on water and electrolyte transport in the distal tubule were investigated by micropuncture. Since, in addition to antidiuretic hormone, parathyroid hormone, calcitonin and glucagon stimulate the adenylate-cyclase system in this nephron segment, experiments were performed on hormone-deprived rats, i.e. homozygous DI Brattleboro rats with reduced levels of endogenous parathyroid hormone, calcitonin and glucagon. Along the distal tubule, dDAVP enhanced water, Cl, Na and Ca reabsorption and sharply increased net K secretion. Phosphate transport was left unchanged and Mg reabsorption was not significantly altered by dDAVP between the early and late distal tubule. Antidiuretic hormone also slightly increased water filtration rate in the superficial nephron, which rose in proportion to whole kidney glomerular filtration rate. It is concluded that, in rats: antidiuretic hormone stimulates water, NaCl and Ca absorption and enhances K secretion along the distal tubule and the tubular effects of dDAVP on electrolyte transport in the loop and distal tubule are responsible for decreasing Mg and Ca urinary excretion.
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PMID:Effects of antidiuretic hormone on electrolyte reabsorption and secretion in distal tubules of rat kidney. 647 69

The influence of detergents on fluoride- and vanadate-stimulated adenylate cyclases was investigated with enzyme from liver and adipocyte plasma membranes. Stimulation of the adipocyte cyclase by Na3VO4 was maximal (sixfold) at 3 mM, was not additive with fluoride stimulation, and was readily reversed by washing of the membranes. Vanadate stimulation of the hepatic cyclase was specifically blocked by catechol, which had no effect on basal activity or on fluoride- or glucagon-stimulated activities. The hepatic enzyme, stimulated by fluoride ion, guanyl-5'-yl-(beta,gamma-imino)diphosphate (GPP(NH)P), or GPP(NH)P and glucagon, was inhibited by vanadate with 50% inhibition seen with 2 to 6 mM vanadate. The fluoride-activated adipocyte adenylate cyclase was inhibited by guanosine 5'-O-(3-thio-triphosphate) (GTP gamma S) more potently than by GPP(NH)P, with 50% inhibition being seen with 10 nM GTP gamma S or 100 nM GPP(NH)P. These nucleotides also inhibited the vanadate-stimulated enzyme, but with one-third the potency seen with the fluoride-activated cyclase. Dispersion of the adipocyte cyclase by Lubrol-PX into a 30,000g supernatant fraction caused no change in activation of the enzyme by fluoride, but reduced vanadate-stimulated activity 80%. By comparison, this treatment enhanced stimulation by GPP(NH)P twofold and by GTP gamma S threefold. More importantly, perhaps, the treatment with detergent blocked inhibition of the basal enzyme by GTP, blocked inhibition of fluoride- and vanadate-stimulated cyclases by GTP, GPP(NH)P, or GTP gamma S, and rendered vanadate-stimulated activity sensitive to enhancement by guanine nucleotides. The data indicate differences in the actions of vanadate and fluoride, made evident by the influence of guanine nucleotides and detergent treatment. The observations would be consistent with the idea that the effects of vandate may be due to the formation of GDP X V on the enzyme. The data strongly suggest that treatment of adenylate cyclase with Lubrol-PX causes a functional blockade in the guanine nucleotide-dependent inhibitory regulation (mediated by Ni), thereby allowing activation by the stimulatory guanine nucleotide-dependent regulatory component (Ns).
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PMID:Detergent-induced distinctions between fluoride- and vanadate-stimulated adenylate cyclases and their responses to guanine nucleotides. 655 48

The influence of extracellular matrix components, insulin, and glucagon on the cellular response to periportal- or pericentral-equivalent tissue oxygen tension was investigated in freshly isolated rat hepatocytes cultured at 13% O2 or 4% O2 in Teflon membrane dishes. With extended culture time, significant increases in lactate release and cellular lactate content were observed in cultures at 4% O2 compared with 13% O2. This shift toward glycolysis was detectable when hepatocytes were cultured on dishes coated with rat liver crude membrane fraction (CMF/COL) but not in collagen type I-coated dishes. This indicates that extracellular matrix components are involved in the process of adaptation. ATP and total adenylate content in cells cultured at 4% O2 were up to 40% lower than in cells cultured at 13% O2. However, the adenylate energy charge was not affected, suggesting that an adequate energy supply was maintained also in hepatocytes cultured at pericentral-equivalent oxygen tension. This adaptation was reversible. When hepatocytes were transferred either from 4% to 13% O2 or from 13% to 4% O2, they adapted the corresponding metabolic profile to the new oxygen tension within 2 days. This demonstrates that hepatocytes are not fully unidirectionally programmed. The modulation of the glycolytic activity by insulin and glucagon was effective in cultures at pericentral-equivalent oxygen tension (4% O2) only. Insulin (0.1-100 nM) shifted cellular metabolism toward the glycolytic pathway and glucagon (1-100 nM) counteracted the effect of insulin in a dose-dependent manner. Clearly, oxygen tension is the principal regulator in the hepatic glycolytic activity, whereas the hormones (insulin and glucagon) act as secondary modulators.
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PMID:Cultured rat hepatocytes adapt their cellular glycolytic activity and adenylate energy status to tissue oxygen tension: influences of extracellular matrix components, insulin and glucagon. 804 Jan 92

Chrysemys picta bellii is well known for its ability to survive extended anoxic periods and has been widely used as a model system to study anoxic metabolism. Described here is a method for the isolation of anoxia-tolerant hepatocytes from this species. Freshly isolated hepatocytes were determined to be viable based on trypan blue exclusion, gluconeogenic capacity from [14C]lactate, responsiveness to epinephrine and glucagon, and maintenance of cellular adenylate concentrations. Under anoxic conditions for 10 h there was no significant increase in cell staining and no decrease in cellular ATP concentration. Furthermore, the addition of cyanide at the 5-h mark did not result in any significant differences in these parameters; however, iodoacetate added at this time caused trypan blue staining to increase and ATP concentrations to fall. The rate of glucose production from the cells was threefold greater under anoxic than normoxic conditions, underscoring the important role of the liver in supplying substrate during anoxia. From the rate of O2 consumption and rate of lactate production under anaerobic conditions, ATP turnover rates were calculated to be 68.4 +/- 7.2 and 6.5 +/- 0.43 mumol ATP.g-1.h-1, respectively; this corresponds to a 90% decrease in metabolic rate during anoxia. Within a cellular system such as this the more complex regulatory mechanisms involved in a large coordinated reduction in metabolism can be probed.
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PMID:Anoxia-tolerant hepatocytes: model system for study of reversible metabolic suppression. 834 99

A cDNA that codes for two peptides in the glucagon superfamily has been isolated from sockeye salmon brain. The first peptide is related to growth hormone-releasing hormone (GHRH), which has high sequence similarity with PACAP-related peptide. The second peptide is structurally related to vasoactive intestinal peptide, which is also related to a newly identified peptide in mannals, pituitary adenylate-cyclase-activating polypeptide (PACAP). The salmon precursor contains 173 amino acids and has dibasic and monobasic enzyme-processing sites for cleavage of a 45-amino-acid GHRH-like peptide with a free C-terminus and a 38-amino-acid PACAP with an amidated C-terminus. The salmon GHRH-like peptide has 40% amino acid sequence identity with a human GHRH and 56% identity with human PACAP-related peptide. The 38-amino-acid salmon PACAP is highly conserved (89-92% identity) with only three or four amino acid substitutions compared with the human, ovine and rat 38-amino-acid PACAP. Not previously reported for mammalian species, a short precursor coding for only one peptide exists in salmon in addition to the long precursor coding for two peptides. In the short precursor, the coding region for GHRH is deleted leaving the PACAP-coding region in a correct reading frame. This provides one possible control mechanism for an increased expression of one peptide (PACAP) without the concomitant increase in the other peptide (GHRH) as occurs in a double-peptide precursor. The importance of the 3' non-translated region of the salmon GHRH/PACAP precursor in the regulation of translation is suggested by its 70% nucleotide sequence identity to the 3' non-translated regions of the mammalian PACAP precursors. The structural organization of the salmon GHRH/PACAP precursor provides a possible evolutionary scheme for precursors that contain tandem peptides in the glucagon superfamily.
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PMID:Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily. 834 11

The presence of glucagon receptors on human adipocytes has not yet been described. In this work we present an exceptional case of glucagon binding to human adipocytes taken from a malignant tumor of adipose tissue of a patient with a liposarcoma. Binding analysis revealed that the total number of glucagon receptors on liposarcoma-cells was 99,000 and the apparent receptor affinity (ED:50) was 5 x 10(-9) M. Despite the presence of these specific receptors, glucagon was unable to induce a lipolytic response, or to activate the adenylate-cyclase system in these liposarcoma-cells. Whether the induction of glucagon receptors is a specific process of the tumor biology remains to be elucidated.
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PMID:Identification of glucagon receptors in human adipocytes from a liposarcoma. 839 2

The present study was designed to define whether maximal removal rate of indocyanine green (ICG Rmax), plasma cyclic 3',5'-adenosine monophosphate (cAMP) response to exogenous glucagon (peak to basal ratio of cAMP level: P/B cAMP) and plasma half-life of galactose (t1/2 galactose) can measure the hepatic functional reserve of fatty liver prepared in rats fed choline-deficient (9 weeks), 2% cholesterol (2 weeks) or 0.25% DL-ethionine (2 weeks) diet. Although changes in cholesterol and phospholipid values in serum during feeding periods differed among the models, histopathologic examinations in the liver of almost all animals revealed intermediate to severe fatty liver with or without fibrosis at each termination. ICG Rmax and P/B cAMP were significantly decreased in rats fed choline-deficient or DL-ethionine diet, implying reductions in hepatic functional mass and disturbances in hepatic cAMP production. Meanwhile, t1/2 galactose showed no change in any of the models, suggesting that glucose metabolisms in the models used may be preserved. These findings demonstrate that ICG Rmax and P/B cAMP can apply to measurement of hepatic surviving reserve of fatty liver with fibrosis.
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PMID:Application of hepatic tolerance tests to the functional reserve assessment in rat models of fatty liver. 963 1

Recent progress in research on pituitary adenylate-activating polypeptide (PACAP) with a special emphasis on the brain is reviewed. PACAP is a pleiotropic neuropeptide that belongs to the secretin/glucagon/vasoactive intestinal peptide family. PACAP functions as a hypothalamic hormone, neurotransmitter, neuromodulator, and neurotrophic factor. Studies on the gene encoding the PACAP precursor and the specific PACAP receptor (PAC1-R) and its subtypes have provided information on the control of gene expression for PACAP, and the relationship between the receptor subtypes and the signal transduction pathways. The PAC1-R is a G protein-coupled receptor with seven transmembrane domains and belongs to the VIP receptor family. At least eight subtypes of PAC1-R result from alternate splicing. Each subtype is coupled to specific signaling pathways, and its expression is tissue or cell specific. PACAP stimulates the release of arginine vasopressin and increases cytosolic Ca2+ ([Ca2+]i). PACAP serves as a neurotransmitter and/or neuromodulator and the activation of the PAC1-R stimulates a cAMP-protein kinase A signal transduction pathway which in turn evokes the [Ca2+]i signaling system. More importantly, PACAP is a neurotrophic factor that may play an important role during the development of the brain. The PAC1-R is actively expressed in different neuroepithelia from early developmental stages and expressed in various brain regions during prenatal and postnatal development. In the adult brain, PACAP appears to function as a neuroprotective factor that attenuates the neuronal damage resulting from various insults.
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PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in the brain. 1119 92

The cooperative effect of glucagon-like peptide 1 (GLP-1) and acetylcholine (ACh) was evaluated in a beta cell line model (BRIN BD11). GLP-1 (20 nM) and ACh (100 microM) increased insulin secretion by 24-47%, whereas in combination there was a further 89% enhancement of insulin release. Overnight culture with 100 ng/mL pertussis toxin (PTX) or 10nM PMA significantly reduced the combined insulinotropic action (P<0.05 and P<0.001, respectively) and the sole stimulatory effects of GLP-1 (PTX treatment; P<0.01) or ACh (PMA treatment; P<0.05). Under control conditions, ACh (50nM-1mM) concentration-dependently inhibited by up to 40% (P<0.001) the 10-fold (P<0.001) elevation of cyclic 3',5'-adenosine monophosphate (cAMP) induced by 20 nM GLP-1. The paradoxical inhibitory action of ACh was abolished by PTX pre-treatment, suggesting involvement of G(i) and/or G(o) G protein alpha subunit. Effects of selective muscarinic receptor antagonists on the concentration-dependent insulinotropic actions of ACh (50 nM-1 mM) on 20 nM GLP-1 induced insulin secretion revealed inhibition by rho-FHHSiD (M3 antagonist, P<0.05), stimulation with pirenzepine (M1 antagonist, P<0.001) and no significant effects of either methoctramine (M2 antagonist) or MT-3 (M4 antagonist). Antagonism of M2, M3 and M4 muscarinic receptor effects with methoctramine (3-100 nM), rho-FHHSiD (3-30 nM) or MT-3 (10-300 nM) did not significantly affect the inhibitory action of ACh on GLP-1 stimulated cAMP production. In contrast, M1 receptor antagonism with pirenzepine (3-30 0nM) resulted in a concentration-dependent decrease in the inhibitory action of ACh on GLP-1 stimulated cAMP production (P<0.001). These data indicate an important functional cooperation between the cholinergic neurotransmitter ACh and the incretin hormone GLP-1 on insulin secretion mediated through the M3 muscarinic receptor subtype. However, the insulinotropic action of ACh was associated with a paradoxical inhibitory effect on GLP-1 stimulated cAMP production, achieved through a novel PTX- and pirenzepine-sensitive M1 muscarinic receptor activated pathway. An imbalance between these pathways may contribute to dysfunctional insulin secretion.
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PMID:Cooperative enhancement of insulinotropic action of GLP-1 by acetylcholine uncovers paradoxical inhibitory effect of beta cell muscarinic receptor activation on adenylate cyclase activity. 1250 4

Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory. Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation. Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition. The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy. A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.
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PMID:Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry? 1508 83


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